Tetrahydrofuran → Ethyl 2-(4-amino-5-{4-[({[4-(trifluoromethyl)pyridin-2-yl]amino}carbonyl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazin-6-yl)-4,5-dihydro-1,3-oxazole-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of THF (2 mL) was added ethyl N-[(4-amino-5-{4-[({[4-(trifluoromethyl)pyridin-2-yl]amino}carbonyl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazin-6-yl)carbonyl]serinate (Example 221) (50 mg, 0.09 mmol) which was cooled to −78° C. DAST (13 μL, 0.10 mmol) was added and the reaction proceeded for 1 h while stirring under N2. Anhydrous K2CO3 was then added and the solution was allowed to warm to rt over the following 30 min. The reaction mixture was transferred to a separatory funnel, diluted with EtOAc (20 mL), washed with aq saturated NaHCO3 (20 mL) and H2O (20 mL). The organic was collected, dried (MgSO4), and evaporated in vacuo. The crude material was purified by preparative HPLC (10-90% ACN/H2O with 0.1% TFA). The fractions were left overnight resulting in the partial formation of a new product. The two products were separated by column chromatography 5:4:1 v/v/v DCM/EtOAc/MeOH resulting in the isolation of 9 mg of the title compound (0.016 mmol, 18%). 1H-NMR (DMSO-d6) δ 9.91 (s, 1H), 9.78 (s, 1H), 8.54 to 8.53 (d, J=5.0 Hz, 1H), 8.08 (s, 1H), 8.05 (s, 1H), 7.91 (s, 1H), 7.58 to 7.56 (d, J=8.6 Hz, 2H), 7.37 to 7.36 (d, J=5.1 Hz, 1H), 7.34 to 7.32 (d, J=8.6 Hz, 2H), 4.75 to 4.71 (m, 1H), 4.38 to 4.29 (m, 2H), 4.13 to 4.08 (q, J=7.1 Hz, 2H), 1.21 to 1.18 (t, J=7.0 Hz, 3H); MS [M+H]+=555.1; LCMS RT=2.84 min.

Provenance & Evidence